POS0753 TIF1-GAMMA IGG2 ISOTYPE IS ASSOCIATED WITH ETHNICITY IN JDM PATIENTS
Authors: H. Nguyen, F. Jouen, B. Déchelotte, N. Cordel, C. Gitiaux, C. Bodemer, P. Quartier, A. Belot, K. O’brien, I. Melki, N. Fabien, S. Tansley, L. Wedderburn, O. Boyer, B. Bader-Meunier
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Dermatomyosis is an autoimmune disease that can present in children, adolescents (juvenile dermatomyosis JDM), and adults (adult dermatomyositis DM). The pathological hallmarks of DM are similar between JDM and adult DM, including skin rashes and proximal muscle weakness, however, the manifestations and prevalence of associated autoantibodies vary, depending on age of onset. Myositis specific antibodies (MSA) have been used as a prognostic tool to aid management of disease in both adult DM and JDM. In JDM, anti-TIF1γ is highly prevalent, and is the most common MSA in Caucasian patients. This MSA is associated with malignancy in adult DM [1]. We have previously shown that adult DM patients with cancer have significantly higher frequency and serological level of anti-TIF1γ IgG2 isotype [2]. However, there are limited data on anti-TIF1γ isotypes in JDM. <h3>Objectives</h3> To investigate anti-TIF1γ isotypes as a potential biomarker for clinical manifestations in JDM. <h3>Methods</h3> We conducted a retrospective study to evaluate clinical features of anti-TIF1γ positive patients. This cohort includes 20 patients from French healthcare centres and 11 patients from the UK healthcare centres. Serum samples were first tested for anti-TIF1γ using either lineblot or immunoprecipitation. Within those with anti-TIF1γ antibodies, anti-TIF1γ isotypes including IgG1, IgG2, IgG3 and IgG4 were measured using a multiplex ALBIA assay developed by Aussy et al. (2019) [2]. <h3>Results</h3> Out of 31 children, 54.8% (17) were Caucasian, followed by North African (25.8%, n=7), and other minority groups. Male to female ratio was 14/17. All 31 patients had IgG1 isotype, and 14 had more than one isotype of anti-TIF1γ antibody. Although IgG2 isotype of anti-TIF1γ has been shown to be a biomarker for malignancy and mortality in adult DM, there were no reports of malignancy in this paediatric cohort. In our JDM cohort, the rate of IgG2-positive was 25.8% (8/31) which is lower than observed in adult DM of 55% [2]. Two cases in this JDM cohort died: both were positive for IgG4, but both were negative for IgG2. Interestingly, there were significant differences regarding IgG2 isotype of anti-TIF1γ antibody presence between ethnic groups (p = 0.008). Specifically, although Caucasian patients were the majority, only 1 out of 8 IgG2 positive cases was Caucasian. Between Caucasian and non-Caucasian groups, significant differences were observed when comparing the groups' means (p = 0.02) and variances (p = 0.01). Notably, 4/8 IgG2 positive were found in North African population, making up 44.4% (4/9) of this ethnic group. We also showed that anti-TIF1γ isotypes can change over time. Specifically, of 6 patients tested for anti-TIF1γ isotypes at a second time point, 4 cases had changes in serological levels of anti-TIF1γ isotypes: 2 had lower titer levels, 1 lost positive status for IgG2 and IgG3, and 1 gained positive status for IgG4. <h3>Conclusion</h3> Our study indicates that there may be a relationship between anti-TIF1γ IgG2 isotype and ethnicity. Importantly, although IgG2 is a biomarker for cancer in adult DM, it is not associated with severe onset or manifestations such as mortality or malignancy in JDM patients. <h3>References</h3> [1]Cordel N, Dechelotte B, Jouen F, Lamb JA, Chinoy H, New P, Vencovsky J, Mann H, Galindo-Feria AS, Dani L, Selva-O'Callaghan A, Werth VP, Ravishankar A, Landon-Cardinal O, Tressières B, Boyer O. Anti-transcription intermediary factor 1-gamma IgG2 isotype is associated with cancer in adult dermatomyositis: an ENMC multinational study. Rheumatology (Oxford). 2022 Oct 17:keac577. doi: 10.1093/rheumatology/keac577. Epub ahead of print. [2]Aussy A, Fréret M, Gallay L, Bessis D, Vincent T, Jullien D, Drouot L, Jouen F, Joly P, Marie I, Meyer A, Sibilia J, Bader-Meunier B, Hachulla E, Hamidou M, Huë S, Charuel JL, Fabien N, Viailly PJ, Allenbach Y, Benveniste O, Cordel N, Boyer O; OncoMyositis Study Group. The IgG2 Isotype of Anti-Transcription Intermediary Factor 1γ Autoantibodies Is a Biomarker of Cancer and Mortality in Adult Dermatomyositis. Arthritis Rheumatol. 2019 Aug;71(8):1360-1370. doi: 10.1002/art.40895. Epub 2019 Jul 8. <h3>Acknowledgements</h3> We thank all research coordinators, principal inestigators, patients and their families who have contributed to this research. <h3>Disclosure of Interests</h3> Huong Nguyen: None declared, Fabienne Jouen: None declared, Benoit Déchelotte: None declared, Nadege Cordel: None declared, cyril gitiaux: None declared, christine bodemer: None declared, Pierre Quartier: None declared, alexandre belot: None declared, Kathryn O'brien: None declared, isabelle melki: None declared, Nicole Fabien: None declared, Sarah Tansley: None declared, Lucy Wedderburn Consultant of: Pfizer, olivier boyer Consultant of: Argenx, BMS, CSL Behring, Egle Tx, OGD2, UCB, Grant/research support from: Argenx, UCB, Brigitte Bader-Meunier: None declared.